SOCS3_BOVIN
ID SOCS3_BOVIN Reviewed; 229 AA.
AC Q9BEG9;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Suppressor of cytokine signaling 3;
DE Short=SOCS-3;
GN Name=SOCS3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hirano A., Norimine J., Brown W.C.;
RT "Cloning of bovine suppressor of cytokine signaling-3.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: SOCS family proteins form part of a classical negative
CC feedback system that regulates cytokine signal transduction. SOCS3 is
CC involved in negative regulation of cytokines that signal through the
CC JAK/STAT pathway. Inhibits cytokine signal transduction by binding to
CC tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin,
CC insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its
CC kinase activity and regulates IL6 signaling. Suppresses fetal liver
CC erythropoiesis. Regulates onset and maintenance of allergic responses
CC mediated by T-helper type 2 cells (By similarity). Probable substrate
CC recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins (By similarity). {ECO:0000250|UniProtKB:O14543,
CC ECO:0000250|UniProtKB:O35718}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with multiple activated proteins of the tyrosine
CC kinase signaling pathway including IGF1 receptor, insulin receptor and
CC JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a
CC phosphorylated tyrosine residue within the JAK2 JH1 domain. Binds
CC specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and
CC gp130 receptors. Interaction with CSNK1E stabilizes SOCS3 protein.
CC Component of the probable ECS(SOSC3) E3 ubiquitin-protein ligase
CC complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SOCS3.
CC Interacts with CUL5, RNF7, ELOB and ELOC. Interacts with FGFR3.
CC Interacts with INSR. Interacts with BCL10; this interaction may
CC interfere with BCL10-binding with PELI2. Interacts with NOD2 (via CARD
CC domain); the interaction promotes NOD2 degradation.
CC {ECO:0000250|UniProtKB:O14543, ECO:0000250|UniProtKB:O35718}.
CC -!- DOMAIN: The ESS and SH2 domains are required for JAK phosphotyrosine
CC binding. Further interaction with the KIR domain is necessary for
CC signal and kinase inhibition.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues after stimulation by the
CC cytokines, IL-2, EPO or IGF1. {ECO:0000250}.
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DR EMBL; AY026859; AAK07689.1; -; mRNA.
DR RefSeq; NP_776891.1; NM_174466.2.
DR RefSeq; XP_005221196.1; XM_005221139.3.
DR AlphaFoldDB; Q9BEG9; -.
DR BMRB; Q9BEG9; -.
DR SMR; Q9BEG9; -.
DR STRING; 9913.ENSBTAP00000011106; -.
DR PaxDb; Q9BEG9; -.
DR Ensembl; ENSBTAT00000011106; ENSBTAP00000011106; ENSBTAG00000008441.
DR GeneID; 282081; -.
DR KEGG; bta:282081; -.
DR CTD; 9021; -.
DR VEuPathDB; HostDB:ENSBTAG00000008441; -.
DR VGNC; VGNC:35121; SOCS3.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000159620; -.
DR HOGENOM; CLU_079452_3_0_1; -.
DR InParanoid; Q9BEG9; -.
DR OMA; KLVHYYM; -.
DR OrthoDB; 1135696at2759; -.
DR TreeFam; TF321368; -.
DR Reactome; R-BTA-1059683; Interleukin-6 signaling.
DR Reactome; R-BTA-877300; Interferon gamma signaling.
DR Reactome; R-BTA-877312; Regulation of IFNG signaling.
DR Reactome; R-BTA-8849474; PTK6 Activates STAT3.
DR Reactome; R-BTA-8951664; Neddylation.
DR Reactome; R-BTA-909733; Interferon alpha/beta signaling.
DR Reactome; R-BTA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-BTA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000008441; Expressed in intramuscular adipose tissue and 101 other tissues.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0035198; F:miRNA binding; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0097398; P:cellular response to interleukin-17; IEA:Ensembl.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0060674; P:placenta blood vessel development; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:InterPro.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR CDD; cd10384; SH2_SOCS3; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028414; SOCS3.
DR InterPro; IPR035863; SOCS3_SH2.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF11; PTHR10155:SF11; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 2: Evidence at transcript level;
KW Growth regulation; Phosphoprotein; Reference proteome; SH2 domain;
KW Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..229
FT /note="Suppressor of cytokine signaling 3"
FT /id="PRO_0000181241"
FT DOMAIN 46..142
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 181..228
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 22..33
FT /note="Kinase inhibitory region (KIR)"
FT REGION 34..45
FT /note="Extended SH2 subdomain (ESS)"
FT REGION 132..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..162
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 229 AA; 25134 MW; 263969074012D7C8 CRC64;
MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWST VTGGEANLLL
SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG SFSLQSDPRS TQPVPRFDCV
LKLVHHYMPA AGAPSFSQPP AEPSSSPSSE VPEQPPAQPL SGNPPRRAYY IYSGGEKIPL
VLSRPLSSNV ATLQHLCRKT VNGHLDSYEK VTQLPGPIRE FLDQYDAPL
